Immunology and Infectious Disease Commons^™

Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with helminth parasites causes morbidity and mortality in billions of people and livestock worldwide. Where anthelmintic drugs are available, drug resistance is a major problem in livestock parasites, and a looming threat to public health. Monitoring the efficacy of these medicines and screening for new drugs has been hindered by the lack of objective, high-throughput approaches. Several cell monitoring technologies have been adapted for parasitic worms, including video-, fluorescence-, metabolism enzyme- and impedance-based tools that minimize the screening bottleneck. Using the xCELLigence impedance-based system we previously developed a motility-viability assay that is applicable for a range of helminth parasites. …

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and …

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …

Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV …

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …

Development Of A Biosensor-Based Rapid Urine Test For Detection Of Urogenital Schistosomiasis., Kathleen E Mach, Ruchika Mohan, Shailja Patel, Pak Kin Wong, Michael Hsieh, Joseph C Liao

Urology Faculty Publications

No abstract provided.

Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2) …

Hepatitis B Vaccines And Hpv Vaccines Have Been Hailed As Major Public Health Achievements In Preventing Cancer--Could A Schistosomiasis Vaccine Be The Third?, Michael H. Hsieh, Julia M L Brotherton, Afzal A Siddiqui

Urology Faculty Publications

No abstract provided.

A Microrna Profile Associated With Opisthorchis Viverrini-Induced Cholangiocarcinoma In Tissue And Plasma., Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasiteOpisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically …

Opisthorchiasis: An Overlooked Danger, Ludmila M. Ogorodova, Olga S. Fedorova, Banchob Sripa, Viatcheslav A. Mordvinov, Aleksei V. Katokhin, Paul J. Brindley, The Topic Consortium

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Two Potential Hookworm Daf-16 Target Genes, Snr-3 And Lpp-1: Gene Structure, Expression Profile, And Implications Of A Cis-Regulatory Element In The Regulation Of Gene Expression, Xin Gao, Kevin Goggin, Camille Dowling, Jason Qian, John Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection.

Methods

Genomic Fragment 2.23 containing a DAF-16 binding …

The Carcinogenic Liver Fluke Opisthorchis Viverrini Is A Reservoir For Species Of Helicobacter., Raksawan Deenonpoe, Chariya Chomvarin, Chawalit Pairojkul, Yaowalux Chamgramol, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms …

Comparison Of Findings Using Ultrasonography And Cystoscopy In Urogenital Schistosomiasis In A Public Health Centre In Rural Angola, Julio Santos, Jacinta Chaves, Heriberto Araujo, Nuno Vale, Jose Manuel Costa, Paul J. Brindley, Carlos Lopes, Jean Naples, Clive Shiff, Jorge Dupret, Lucio Lara Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Schistosomiasis is a chronic disease caused by infection with parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with S. haematobium are most common. Cystoscopic examination (CE) has been accepted as the gold-standard test for detecting the late manifestations of schistosomiasis, including urothelial cancer of the bladder. However, this procedure is invasive and 10 - 40% of tumours may remain undetected. A non-invasive examination and a new generation of biomarkers are needed for better monitoring of the disease.

Objective. To assess the usefulness of ultrasound (US) scans for monitoring of structural urinary tract disease by local public health …

An Improved Method For Generating Axenic Entomopathogenic Nematodes., Shruti Yadav, Upasana Shokal, Steven Forst, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Steinernema carpocapsae are parasitic nematodes that invade and kill insects. The nematodes are mutualistically associated with the bacteria Xenorhabdus nematophila and together form an excellent model to study pathogen infection processes and host anti-nematode/antibacterial immune responses. To determine the contribution of S. carpocapsae and their associated X. nematophila to the successful infection of insects as well as to investigate the interaction of each mutualistic partner with the insect immune system, it is important to develop and establish robust methods for generating nematodes devoid of their bacteria.

FINDINGS: To produce S. carpocapsae nematodes without their associated X. nematophila bacteria, we …

Gene Function In Schistosomes: Recent Advances Toward A Cure, Arnon D. Jurburg, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Of Monkeys And Men: Immunomic Profiling Of Sera From Humans And Non-Human Primates Resistant To Schistosomiasis Reveals Novel Potential Vaccine Candidates., Mark S Pearson, Luke Becker, Patrick Driguez, Neil D Young, Soraya Gaze, Jeffrey M. Bethony, +12 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well …

Repeated Plasmodium Vivax Malaria Relapses In A Peruvian Sailor., Adam P. Mcfarland, Juan F Sanchez, Alejandro Mercado, Julio A Ventocilla, Sofia Cavalcanti, Sofia Gonzalez, Andres G Lescano

Medicine Faculty Publications

Two Plasmodium vivax recurrences in a Peruvian sailor with weight above the 60 kg (cap for primaquine dosage) highlight the importance of adequate radical cure weight dosage for patient treatment and control efforts, particularly within the military.